INTRODUCTION: Pain generation in the nervous system is strongly associated with TNF‐α. Older adults experience less axial LBP, because these IVD tissues may be less responsive to TNF‐α. It is also believed that IVD degeneration first appears in NP. We aimed to determine divergent responses to TNF‐α by cells that populate the structurally different areas of the IVD, and to establish age‐related variations in sensitivity of these same cells.
METHODS: IVDs from 28 human lumbar spine segments (15‐71years, Pfirrmann grades 1 and 2) were dissected. Cells were isolated from the outer‐AF, inner‐AF, transition zone and NP; treated in monolayers with TNF‐α (100 pg/ml ‐ 10ng/ml), and analyzed for cell signaling (pNF‐?B) and mRNA expression (MMP‐1, MMP‐13). TNF‐α receptor density on the cells was also determined.
RESULTS: Significant differences were found in responsiveness among the cells of the IVD (NP > TZ > iAF >> oAF) 8‐20‐fold higher signals were observed in the NP than in the oAF cells. All cell types showed an age‐dependent decline in sensitivity; the most in the NP and the least in the oAF. These changes were reflected at both signaling and mRNA expression levels. TNF‐receptor levels correlated with the age‐ and locationrelated differences observed above.
DISCUSSION: The NP, particularly sensitive to TNF‐α, may serve as the initial area for degeneration; while the non‐responsive oAF may serve as a barrier to tissue degeneration. When oAF degenerates, it may be ingrown by vascular tissue and nerves that may lead to pain. The reason that older adults experience little pain may well be that the IVD cells become desensitized to inflammatory mediators in aging, potentially through expressing lower levels of receptors. Based upon these findings, translational studies could target specific areas of the disc, and specific molecules/receptors that would prevent further disc degeneration and/or the development of pain.